Treatment of viral influenza infections

ABSTRACT

The administration internally to humans of 1-( Beta hydroxyethyl)-2-methyl-5-nitroimidazole, (metronidazole) in a dosage range for adult humans of about 31 to 1,000 mgs per 24 hour period, is an effective therapeutic treatment for viral influenza infections.

United States Patent [1 1 Mercer [4 1 Dec. 24, 1974 TREATMENT OF VIRAL INFLUENZA INFECTIONS [22] Filed: June 18, 1973 [21] Appl. No.: 370,952

[52] U.S. Cl. 424/273 [51] Int. Cl A61k 27/00 [58] Field of Search 424/273 [56] References Cited OTHER PUBLICATIONS Cecil et al., A Textbook of Medicine, W. B. Saunders C0., Phila., Pa., 1958, page I.

The Merck Index, 8th Ed., Merck & C0., lnc., Rahway, N.J., 1968, page 695.

Primary Examiner.lerome D. Goldberg Attorney, Agent, or FirmFishburn, Gold & Litman [57] ABSTRACT The administration internally to humans of l-(B- hydroxyethyl)-2-methyl-5-nitroimidazole, (metronidazole) in a dosage range for adult humans of about 3] to 1,000 mgs per 24 hour period, is an effective therapeutic treatment for viral influenza infections.

3 Claims, N0 Drawings TREATMENT OF VIRAL INFLUENZA INFECTIONS The invention herein described relates to a method of treating viral influenza infections.

The objects of this invention are: to provide a method for systematically treating viral influenza infections in humans; to provide such a treatment which is effective; to provide such a method that is suitable for intensive therapy as well as long term maintenance and intermittant therapy, and to provide such a treatment which is usually well tolerated by the recipient.

l-( B-hydroxyethyl )-2-methyl-5-nitroimidazole, (metronidazole) is a known alkylating agent of relatively low toxicity which is thought to interfere with nucleic acid biosynthesis. It appears that metronidazole can penetrate all tissues of the body quite readily and its effectiveness, in the treatment of viral influenza infections, is believed to relate to blockage or interference in the viral metabolism cycle necessary for cell infection. Thus, the agent apparently suppresses virus production while natural body defenses function to eliminate viral material from the system. The agent is readily absorbable from the human intestinal tract and may be administered orally as well as by vagina] or rectal inserts, when indicated.

Clinical observations upon the administration of metronidazole in the treatment of viral influenza infections have demonstrated marked patient improvement and in many cases, apparent complete remissions.

A typical intense treatment for an average size adult patient comprises 250 mgs of the agent four times daily for a period of about 4 weeks, then a reduction to 125 mgs. four times daily for several additional weeks and thereafter further reduction depending upon the tolerance of the patient and absence of symptoms. Doses for children are proportionally less according to body weight.

An ultimate effective long-term maintenance dose was found to be as low as 3] mgs per day. The most common effective maintenance dose has been determined to be about 125 mgs per day for a substantial percentage of the patients with 250 mgs per day being indicated and well tolerated for other patients, depending on age, size, and physical condition. A reasonable maximum dosage for adult humans appears to be about 1,000 mgs per day. A renewal of treatment has been found to be effective upon a return of symptoms after treatment was discontinued.

Regarding side effects, some persons were found to experience nausea but it generally disappeared after a few weeks. In rare instances there was a slight soreness of the mouth or a white tongue indicating dosage reduction. Some dizziness and dryness of the mouth and vagina were occasionally noted and a few persons complained of a bad taste. Also, moderate leukopenia was occasionally observed, which normally returned to normal after dosage reduction or completion of a treatment regiman or as therapy continues.

Metronidazole is believed contraindicated in patients under treatment with desulfadram (Antabuse) and in uncompensated hypothyroid patients. Because metronidazole appears to cross the placental barrier and enter the fetal circulation rapidly and further since its effect on fetal development are not definitely known, it is also thought to be contraindicated during the first trimester of pregnancy, except when a history of prior existing viral infection tends to endanger that pregnancy.

The initial neurological signs of metronidazole overdose in humans appear to be increased pulse rate, difficulty in reading small print, difficulty in handling small objects and insomnia. Progressively, it is understood that tachycardia may occur, and a slightly unstable person, especially, may suffer marked swings in mood. Physical exercise apparently becomes increasingly fatiguing, and weight loss occurs to spite substantial food intake. When the medication is withdrawn, the adverse reaction usually clears in 1 week.

The metronidazole treatment described does not appear to damage the hematopoietic or the reticuloendothelial systems.

Over the past several years metronidazole has been tried with various effectiveness for the treatment of trichomonas vaginalis infections, alcoholism, ameobic dysentery, ameobic liver abscess, leishmaniasis and giardia infestations, acute ulcerative gingivitis, long standing indolent ischemic ulcers found in peripheral vascular disease, scleroderma, schizophrenia and in diabetic retinopathy, but apparently its effectiveness in viral influenza infections has not been known.

Metronidazole apparently interferes directly with the synthesis of the DNA viruses, in a similar manner that occurs with cytosine arabinoside. Metronidazole also apparently interferes with protein synthesis, as uric acid levels increase during therapy and may in some instances manifest itself in acute gout.

It is to be understood that while certain practices of this invention have been described herein, it is not to be limited to the specific form described except insofar as such limitations are included in the following claims.

What is claimed and desire to secure by Letters Patent is:

1. A method for the treatment of viral influenza infections in a human host, comprising: administering orally an anti-viral influenza infection effective amount of l-(B-hydroxyethyl)-2-methyl-S-nitromidazole to a human host in need of said treatment.

2. The method of claim 1 wherein; the dosage range of the compound in adult human hosts is about 3] mgs to 1,000 mgs per 24 hour period.

3. The method of claim 1 wherein; said compound is administered to a human host in a dosage of about mgs per 24 hour period. 

1. A METHOD FOR THE TREATMENT OF VIRAL INFLUENZA INFECTIONS IN A HUMAN HOST, COMPRISING: ADMINISTERING ORALLY AN ANTI-VIRAL INFLUENZA INFECTION EFFECTIVE AMOUNT OF 1-(B-HYDROXYETHYL)-2METHYL-5-NITROMIDAZOLE TO A HUMAN HOST IN NEED OF SAID TREATMENT.
 2. The method of claim 1 wherein; the dosage range of the compound in adult human hosts is about 31 mgs to 1,000 mgs per 24 hour period.
 3. The method of claim 1 wherein; said compound is administered to a human host in a dosage of about 125 mgs per 24 hour period. 